Optimization and Application of the QuEChERS-UHPLC-QTOF-MS Method for the Determination of Broflanilide Residues in Agricultural Soils.

In this study, the separation conditions of UHPLC-QTOF-MS and the extraction conditions of QuEChERS were optimized. The analytical process for determining Broflanilide residues in different soil types was successfully established and applied to its adsorption, desorption, and leaching in soil. Broflanilide was extracted from soil with acetonitrile and purified using PSA and MgSO4. The modified UHPLC-QTOF-MS method was used for quantification. The average recovery of Broflanilide was between 87.7% and 94.38%, with the RSD lower than 7.6%. In the analysis of adsorption, desorption, and leaching quantities in four soil types, the RSD was less than 9.2%, showing good stability of the method, which can be applied to determine the residue of Broflanilide in different soils.

Rotenone, an environmental toxin, causes abnormal methylation of the mouse brain organoid's genome and ferroptosis.

More and more reports have pointed out that rotenone, as an insecticide, has high neurotoxicity and reproductive toxicity to livestock and mammals. As a highly physiological correlation system of internal organs, quasi-organs have great potential in the fields of drug toxicity and efficacy test, toxicology research, developmental biology and so on. In this study, brain organs (mBOs) derived from mouse neural stem cells were used to investigate the effects of rotenone on the physiological activity and epigenetic modification of mBOs. At the same time, Rotenone could significantly stimulate the increase of the concentration of LPO, lactic acid and hydroxyl radical in mBOs, and inhibit the expression of neuronal marker Tuj1, CHAT, PAX6 and so on. Further analysis showed that Rotenonem could induce mitochondrial damage in mBOs. The results of qPCR and Western blot showed that Rotenone could up-regulate the expressions of ferroptosis promoting protein p53, Cox2 and so on, while inhibit the expressions of negative regulatory protein of ferroptosis GPX4, FTH1, SLC7A11. In addition, the results of RRBS-Seq sequencing showed that the methylation modification at DMR level in Rotenone-treated mBOs group was significantly higher than that in Ctrl group. The results of KEGG analysis showed that compared with Ctrl, the genes with hypermethylation of promoter and Genebody in Rotenone-treated mBOs were mainly located in the Neuro active ligand-receptor interaction signal transduction pathway. In summary, rotenone can significantly lead to abnormal methylation of mouse brain organs, and lead to the loss of normal physiological function of neurons by inducing ferroptosis.

Atranorin driven by nano materials SPION lead to ferroptosis of gastric cancer stem cells by weakening the mRNA 5-hydroxymethylcytidine modification of the Xc-/GPX4 axis and its expression.

Gastric cancer is a highly malignant tumor. Gastric cancer stem cells (GCSCs) are the main causes of drug resistance, metastasis, recurrence, and poor prognosis. As a secondary metabolite of lichen, Atranorin has a variety of biological effects, such as antibacterial, anti-inflammatory, analgesic, and wound healing; however, its killing effect on GCSCs has not been reported. In this study, we constructed Atranorin complexes comprising superparamagnetic iron oxide nanoparticles (SPION) (Atranorin@SPION). In vitro and in vivo experiments confirmed that Atranorin@SPION could significantly inhibit the proliferation, invasion, angiogenesis, and tumorigenicity of CD44+/ CD24+ GCSCs, and induce oxidative stress injury, Fe2+ accumulation, and ferroptosis. Quantitative real-time reverse transcription PCR and western blotting results showed that Atranorin@SPION not only reduced the expression levels of GCSC stem cell markers and cell proliferation and division markers, but also significantly inhibited the expression levels of key molecules in the cystine/glutamate transporter (Xc-)/glutathione peroxidase 4 (GPX4) and Tet methylcytosine dioxygenase (TET) family proteins. The results of high performance liquid chromatography-mass spectrometry and Dot blotting showed that Atranorin@SPION significantly inhibited the mRNA 5­hydroxymethylcytidine modification of GCSCs. Meanwhile, the results of RNA immunoprecipitation-PCR also indicated that Atranorin@SPIONs significantly reduced the 5-hydroxymethylcytidine modification level of GPX4 and SLC7A11 mRNA 3' untranslated region in GCSCs, resulting in a decrease in their stability, shortening their half-lives and reducing translation activity. Therefore, this study revealed that Atranorin@SPIONs induced ferroptosis of GCSCs by weakening the expression of the Xc-/GPX4 axis and the 5-hydroxymethylcytidine modification of mRNAs in the pathway, thereby achieving their therapeutic effect on gastric cancer.

Agonism of GPR39 displays protective effects against advanced glycation end-product (AGE)-induced degradation of extracellular matrix in human SW1353 cells.

Excessive degradation of the cartilage articular extracellular matrix (ECM) in chondrocytes has been considered as an important pathological characteristics of OA. In the present study, we demonstrate that the G protein-coupled receptor GPR39 is expressed on SW1353 chondrocytes and is significantly downregulated in response to advanced glycation end products (AGEs). Our findings show that agonism of GPR39 exerts significant protective effects against AGE-induced degradation of articular extracellular matrix. Agonism of GPR39 rescued degradation of type II collagen by decreasing expression of the collagen-degrading enzymes matrix metalloproteinase (MMP)-3 and MMP-13. Additionally, agonism of GPR39 rescued AGE-induced suppression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Agonism of GPR39 prevented degradation of aggrecan by downregulating AGE-induced expression of a disintegrin and metalloproteinase with type I thrombospondin motif (ADAMTS)-4 and ADAMTS-5. Finally, we demonstrate that the effects of GPR39 are mediated through the p38 mitogen activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) cellular signaling pathway. Taken together, our findings show for the first time that targeted therapies involving GPR39 may provide a novel approach for the prevention and treatment of osteoarthritis.

The development and evaluation of a sub-health self-rating scale for university students in China.

BACKGROUND: Sub-health status is defined as declines in vitality, physiological function and capacity for adaptation, but without the presence of clinical or sub-clinical disease. We have developed and evaluated a comprehensive questionnaire, the Sub-Health Self-Rating Scale (SSS), to assess sub-health status in university students. METHOD: The items for the draft questionnaire were discussed in focus groups. The WHOQOL-BREF was selected as the validity reference. From a professional perspective and large sample evaluation, the scale ultimately consisted of 58 items. The reliability and validity of the SSS was examined in undergraduate students and 1000 questionnaires were randomly selected from the samples for expert evaluation. RESULTS: Cronbach's α of the total scale was 0.942. The dimensions of physiological, psychological and social had high reliability: 0.915, 0.856 and 0.850, respectively. Based on scree plot and related theories, there were 10 factors to be extracted. The correlation coefficient between the total scale and sub-scale was high. The dimensions of physiological, psychological and social had high correlations with the total scale: 0.929, 0.803 and 0.774, respectively. The sub-health cut-off point of the total scale was 72; for the physiological field, it was 72; for the psychological field, it was 60; and the social field, it was 56. The fit between the expert evaluation method and the scale method was 0.758. The lower the score, the worse the health condition. CONCLUSION: We established and evaluated a valid instrument (SSS) that encompasses physiological, psychological and social factors to investigate sub-health status. It is short and easy to complete, and therefore suitable for use with undergraduate students.

The effects of short-term high-fat feeding on exercise capacity: multi-tissue transcriptome changes by RNA sequencing analysis.

BACKGROUND: The effects of short-term high fat diets on physiology are elusive and the molecular changes following fat overconsumption remain largely unknown. In this study, we aimed to evaluate exercise capacity in mice fed with a high fat diet (HFD) for 3 days and investigate the molecular mechanisms in the early response to high-fat feeding. METHODS: Exercise capacity was assessed by weight-loaded swimming test in mice fed a control diet (10 kcal% fat) or a HFD (60 kcal% fat) for 3 days. Global gene expression of ten important tissues (brain, heart, liver, spleen, lung, kidney, stomach, duodenum, skeletal muscle and blood) was analyzed using RNA Sequencing. RESULTS: A HFD for just 3 days can induce 71% decrease of exercise performance prior to substantial weight gain (P <0.01). Principle component analysis revealed that differential gene expression patterns existed in the ten tissues. Out of which, the brain, spleen and lung were demonstrated to have more pronounced transcriptional changes than other tissues. Biological process analysis for differentially expressed genes in the brain, spleen and lung showed that dysregulation of peripheral and central immune response had been implicated in the early stage of HFD exposure. Neurotransmission related genes and circulatory system process related genes were significantly down-regulated in the brain and lung, respectively. CONCLUSIONS: Our findings provide new insights for the deleterious effects of high-fat feeding, especially revealing that the lung maybe as a new important target attacked by short-term high-fat feeding.

Reno-protective effect and mechanism study of Huang Lian Jie Du Decoction on lupus nephritis MRL/lpr mice.

BACKGROUND: Huang Lian Jie Du Decoction (HLJDD), a very famous traditional Chinese medicinal prescription, has been used for heat dissipation and detoxification in China. This study was aimed to evaluate the reno-protective effects of HLJDD against lupus nephritis (LN) in vivo in MRL/lpr mice. METHODS: Animals were administered orally every day for eight consecutive weeks except the mice of normal group and model group. Organ indexes, serum interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-gamma (IFN-γ) and the anti-double stranded DNA (anti-dsDNA) antibody were tested, respectively. Creatinine (Cr), blood urea nitrogen (BUN) and urine protein were measured for renal function evaluation. The expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT 3) in kidney tissue was observed by western blot (WB) and immunohistochemical (IHC) method. Meanwhile, histopathological changes in the renal were studied by hematoxylin-eosin (H&E) staining. RESULTS: The mice of HLJDD-treated group exhibited a significant reduced mortality (p < 0.05), serum anti-dsDNA level (p < 0.05) and renal immune complex deposition (p < 0.05), compared with the untreated MRL/lpr mice. In addition, HLJDD treatment remarkably reduced the levels of BUN, Cr, proteinuria (p < 0.01) and the levels of inflammatory cytokines such as IL-6, IL-10 and IFN-γ (p < 0.01). Moreover, HLJDD significantly suppressed the phosphorylations of STAT 3 (p < 0.05) and the renal pathological changes. CONCLUSIONS: The study implied that HLJDD may be a potential agent for the therapy of LN, and the down-regulated p-STAT 3 expression suggesting that it may be one of the LN therapy targets for HLJDD.

[Changes of ocular aberration after wavefront-guided aspherical LASIK for myopia].

OBJECTIVE: To compare the higher order aberration of wavefront-guided aspherical versus wavefront-guided and Q-value guided aspheric personalized LASIK surgery in the treatment of myopia. METHODS: Prospective study.120 patients with myopia and/or astigmatism(240 eyes) were involved in our hospital from August 2010 to December 2010. There was a prospective study, divided into three groups: Wavefront-guided aspherical personalized LASIK in group A; Wavefront-guided LASIK in group B; Q-value guided aspheric LASIK in group C. The follow-up time was 6 months. The comparison of data before and after operation was two independent samples t test. The comparison among three groups was one-way analysis of variance, and multiple comparison between groups was Dunnet t test. RESULTS: A group: The differences between before and after surgery were not statistically significant in higher order aberration (t1 week = 0.874, P1 week = 0.387; t1 month = -1.145, P1 month = 0.259; t3 month = 0.652, P3 month = 0.518; t 6 month = 0.496, P6 month = 0.439) , but as the extension of time, The values have a tendency to become smaller; the difference was not statistically significant in spherical aberration between before and after surgery 1 week (t = -1.815, P = 0.077), and was statistically significant between before and after surgery 1 month, 3 months and 6 months after surgery (t1 month = -4.410, P1 month = 0.000; t3 month = -2.375, P 3 month = 0.022; t6 month = -1.870, P 6 month = 0.000) , the values after surgery were higher. The differences between before and after surgery were not statistically significant in coma aberration (t1 week = 1.028, P 1 week = 0.310; t1 month = 0.847, P1 month = 0.402; t3 month = 0.210, P3 month = 0.984; t6 month = 0.533, P6 month = 0.597). At 6 months, the higher order aberration and spherical aberration in A group and C group were significantly lower than the B group, and the differences were statistically significant (P A&B = 0.000; PC&B = 0.000) , the differences between A group and C group were not statistically significant in higher order aberration and spherical aberration(P = 0.866), but A group is less than the C group in changes before and after surgery. The differences among three groups were not statistically significant in the vertical and horizontal coma (Fvertical coma = 0.367, Pvertical coma = 0.683; Fhorizontal coma = 0.254, Phorizontal coma = 0.797). CONCLUSION: Wavefront-guided aspherical personalized LASIK compared with wavefront-guided personalized LASIK can better reduce the increases of the higher order aberration and spherical aberration, and the changes between preoperative and postoperative is less than Q-value guided aspheric personalized LASIK.

Comparative effects of different types of physical activity on health-related quality of life in breast cancer survivors: A systematic review, network meta-analysis, and meta-regression.

Background: Physical activity is associated with improved health-related quality of life (HRQoL) in breast cancer survivors (BCS); however, no studies have assessed optimal physical activity. Objective: We aimed to investigate the optimal types of physical activity for improving HRQoL in patients with BCS during and after cancer treatment. Methods: A comprehensive search was conducted in Medline, Embase, Web of Science, and Cochrane Library from inception to November 2023. We included randomized controlled trials (RCTs) reporting the effects of different physical activities on HRQoL in BCS. Two independent reviewers assessed the risk of bias using the Cochrane risk of bias tool for randomized trials (version 2.0). A network meta-analysis approach based on a frequentist framework was used to rank the effectiveness of different physical activities. Results: A total of 66 RCTs with 6464 participants were included. For all BCS, aerobic combined with resistance exercise (CE) (standardized mean difference [SMD] = 0.71; 95 % confidence interval [CI]: 0.40 to 1.10; P-score = 0.75; Grade: moderate) was the most effective physical activity to improve HRQoL. For participants in treatment, resistance exercise (RE) (SMD = 0.68; 95 % CI: 0.35 to 1.10; P-score = 0.84; Grade: moderate) was the most effective. However, after treatment, CE (SMD = 0.77; 95 % CI: 0.28 to 1.26; P-score = 0.74; Grade: very low) remained the most effective way to improve HRQoL in BCS. In addition, the regression analysis did not find any sources of heterogeneity. Conclusions: The findings of this study suggest that all physical activities improved HRQoL in BCS compared to the control group. CE may have the best effect on all survivors and post-treatment survivors, whereas RE has the best effect during treatment. In addition, the quality of the included studies was low, and there was some risk of bias, which may affect the interpretation of the findings.

Ge-Gen-Qin-Lian decoction alleviates the symptoms of type 2 diabetes mellitus with inflammatory bowel disease via regulating the AGE-RAGE pathway.

BACKGROUND: This study aimed to explore the mechanism of Ge-Gen-Qin-Lian decoction (GGQLD) in the alleviation of symptoms of type 2 diabetes mellitus (T2DM) with inflammatory bowel disease (IBD) by network pharmacology and experimental validation. METHODS: The active components and targets of GGQLD were identified from the TCMSP database. The potential therapeutic targets of T2DM and IBD were identified from the GEO database and 4 online disease target databases. The PPI network and KEGG/GO analyses were performed with the common targets among GGQLD, T2DM and IBD. Molecular docking was carried out between the core compounds and hub targets. To verify the above results, UHPLC-MS technology was used to identify the chemical compounds in GGQLD, and a T2DM with IBD rat model was used to explore the mechanism by which GGQLD treats T2DM with IBD. RESULTS: Totally, 70 potential therapeutic targets were identified among GGQLD, T2DM and IBD. Ten hub genes were selected from the PPI network. KEGG analysis revealed that GGQLD is tightly involved in the AGE-RAGE signaling pathway. Berberine, baicalein, wogonin, and quercitrin are the main active compounds of GGQLD. Animal experiments showed that GGQLD could decrease blood glucose and alleviate intestinal inflammation. Notably, the concentrations of AGEs, the expression of RAGE, c-JUN and NF-κB and the expression of inflammatory cytokines were decreased by GGQLD. CONCLUSIONS: Our study initially demonstrated that GGQLD has favorable anti-hyperglycemic and anti-intestinal inflammation effects in a T2DM with IBD rat model, and the AGE-RAGE pathway plays a vital role in this process.

Cyclocarya paliurus leaves alleviate high-sucrose diet-induced obesity by improving intestinal metabolic disorders.

High-sucrose diets are common in daily life but harmful to human health. Cyclocarya paliurus leaves (CPL) are a kind of tea used to alleviate metabolic diseases and are widely used in China. However, the effects of CPL on high-sucrose-induced obesity are unknown. This study aimed to describe the changes in gut metabolism induced by a high-sucrose diet and to reveal the potential mechanisms through which CPL alleviate high-sucrose diet-induced obesity. A high-sucrose-induced obesity model was generated in C57BL/6J and KM mice. The effects of CPL on obese mice were evaluated, and changes in the gut microbiota and intestinal metabolites induced by CPL treatment were observed. Furthermore, the fecal microbiota transplantation (FMT) method was used to prove that the effects of CPL on high-sucrose induced obesity depend on the changes of gut microbiota. The results of the C57BL/6J mouse experiment revealed that high-sucrose intake induced fat deposition and altered the gut microbiota. CPL treatment decreased fat deposition and alleviated disorders of the gut microbiota. Furthermore, CPL treatment increased the utilization of amnio acids, long fatty acids and saccharides and produced more bile acids, indole derivatives and less trimethylamine (TMA). A confirmatory experiment in KM mice also revealed that CPL can alleviate obesity, ameliorate intestinal metabolic disorders, and upregulate the expression of tight junction proteins in the intestinal mucosa. These results demonstrated that CPL could prevent high sucrose-induced obesity and generate more beneficial intestinal microbial metabolites but less harmful intestinal microbial metabolites.

Arachidonic acid metabolism as a therapeutic target in AKI-to-CKD transition.

Arachidonic acid (AA) is a main component of cell membrane lipids. AA is mainly metabolized by three enzymes: cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP450). Esterified AA is hydrolysed by phospholipase A2 into a free form that is further metabolized by COX, LOX and CYP450 to a wide range of bioactive mediators, including prostaglandins, lipoxins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids. Increased mitochondrial oxidative stress is considered to be a central mechanism in the pathophysiology of the kidney. Along with increased oxidative stress, apoptosis, inflammation and tissue fibrosis drive the progressive loss of kidney function, affecting the glomerular filtration barrier and the tubulointerstitium. Recent studies have shown that AA and its active derivative eicosanoids play important roles in the regulation of physiological kidney function and the pathogenesis of kidney disease. These factors are potentially novel biomarkers, especially in the context of their involvement in inflammatory processes and oxidative stress. In this review, we introduce the three main metabolic pathways of AA and discuss the molecular mechanisms by which these pathways affect the progression of acute kidney injury (AKI), diabetic nephropathy (DN) and renal cell carcinoma (RCC). This review may provide new therapeutic targets for the identification of AKI to CKD continuum.

Erianin Induces Ferroptosis of Renal Cancer Stem Cells via Promoting ALOX12/P53 mRNA N6-methyladenosine Modification.

Renal cell carcinoma (RCC) is the most common type of primary renal parenchymal malignancy in adults, with a high degree of malignancy and poor prognosis. Human renal cancer stem cells (HuRCSCs) are reported to be the main cause of drug resistance, metastasis, recurrence, and poor prognosis. Erianin is a low molecular-weight bibenzyl natural product extracted from Dendrobium chrysotoxum, which inhibits the in vitro and in vivo activity of a variety of cancer cells. However, the molecular mechanisms of Erianin's therapeutic effect on HuRCSCs are unknown. Here, we isolated CD44+/CD105+ HuRCSCs from patients with renal cell carcinoma. The experiments confirmed that Erianin significantly inhibited the proliferation, invasion, angiogenesis, and tumorigenesis of HuRCSCs, and induced oxidative stress injury and Fe2+ accumulation. qRT-PCR and western blotting showed that Erianin significantly reduced the expression levels of cellular Ferroptosis protective factors, and upregulated the expression of METTL3 and downregulated that of FTO. Dot blotting results indicated that Erianin significantly upregulated the mRNA N6-methyladenosine (m6A) modification of HuRCSCs. The results of RNA immunoprecipitation-PCR also indicated that Erianin significantly enhanced the m6A modification level of the 3' untranslated region of ALOX12 and P53 mRNA in HuRCSCs, resulting in increased stability, prolonged half-life, and improved translation activity. In addition, clinical data analysis showed that the expression of FTO correlated negatively with adverse events in patient with renal cell carcinoma. Thus, this study suggested that Erianin can induce Ferroptosis in renal cancer stem cells by promoting N6-methyladenosine modification of ALOX12/P53 mRNA, ultimately achieving a therapeutic effect on renal cancer.

Yi-Shen-Xie-Zhuo formula alleviates cisplatin-induced AKI by regulating inflammation and apoptosis via the cGAS/STING pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Yi-Shen-Xie-Zhuo formula (YSXZF) is a traditional Chinese medicine prescription developed from the classic prescription Mulizexie powder documented in the book of Golden Chamber Synopsis and the Buyanghuanwu Decoction recorded in the book of Correction of Errors in Medical Classics. According to our years of clinical experience, YSXZF can effectively improve qi deficiency and blood stasis in kidney disease. However, its mechanisms need further clarification. AIM OF THE STUDY: Apoptosis and inflammation play key roles in acute kidney disease (AKI). The Yi-Shen-Xie-Zhuo formula, consisting of four herbs, is commonly used for treating renal disease. However, the underlying mechanism and bioactive components remain unexplored. This study aimed to investigate the protective effects of YSXZF against apoptosis and inflammation in a cisplatin-treated mouse model, and identify the main bioactive components of YSXZF. MATERIALS AND METHODS: C57BL/6 mice were administered cisplatin (15 mg/kg) with or without YSXZF (11.375 or 22.75 g/kg/d). HKC-8 cells were treated with cisplatin (20 µM) with or without YSXZF (5% or 10%) for 24 h. Renal function, morphology, and cell damage were evaluated. UHPLC-MS was used to analyze the herbal components and metabolites in the YSXZF-containing serum. RESULTS: Blood urea nitrogen (BUN), serum creatinine, serum and urine neutrophil gelatinase-associated lipocalin (NGAL) levels were clearly increased in the cisplatin-treated group. Administration of YSXZF reversed these changes; it improved renal histology, downregulated kidney injury molecule 1 (KIM-1) expression, and lowered the number of TdT-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells. YSXZF significantly downregulated cleaved caspase-3 and BAX, and upregulated BCL-2 proteins in renal tissues. YSXZF suppressed increase in cGAS/STING activation and inflammation. In vitro treatment with YSXZF markedly reduced cisplatin-induced HKC-8 cell apoptosis, relieved cGAS/STING activation and inflammation, improved mitochondrial membrane potential (MMP), and lowered reactive oxygen species (ROS) overgeneration. Small RNA interference (siRNA)-mediated silencing of cGAS or STING inhibited the protective effects of YSXZF. Twenty-three bioactive constituents from the YSXZF-containing serum were identified as key components. CONCLUSION: This is the first study to demonstrate that YSXZF protects against AKI by suppressing inflammation and apoptosis via the cGAS/STING signaling pathway.

Electroacupuncture attenuates ac4C modification of P16 mRNA in the ovarian granulosa cells of a mouse model premature ovarian failure.

BACKGROUND: Premature ovarian failure (POF) is a type of pathological aging, which seriously interferes with the fertility of affected women. Electroacupuncture (EA) may have a beneficial effect; however, its mechanism of action is unknown. The purpose of this study was to determine the effect of EA on ovarian function in ovarian granulosa cells (OGCs) in a cyclophosphamide (CTX)-induced mouse model of POF. METHODS: Mice were divided into three groups: wild type (WT) group, CTX group and CTX + EA group. EA was administered under isoflurane anesthesia at CV4, ST36 and SP6 for 30 min every 2 days, 2-3 times per week for a total of 4 weeks. Effects of EA on ovarian weight and level of estrogen were examined. The mRNA and protein expression levels of cell cycle-associated proteins were detected and mRNA modifications were analyzed. RESULTS: EA significantly increased ovarian weight and reduced the proportion of atretic follicles in mice with CTX-induced POF (p < 0.05). EA increased the level of estrogen in the peripheral blood of mice and inhibited the modification of total mRNA N4-acetylcytidine (ac4C). A significant increase in the expression of P16 and N-acetyltransferase 10 (NAT10) and a significant decrease in the expression of Cyclin D (CCND1) and cyclin-dependent kinase 6 (CDK6) were observed in the OGCs of POF mice (p<0.05). After EA, P16 and NAT10 expression was decreased, and CCND1 and CDK6 expression was increased. Finally, EA reduced the ac4C modification of P16 mRNA-specific sites in the OGCs of POF mice. CONCLUSION: This study demonstrated that EA promoted the repair of the ovarian microenvironment by inhibiting the ac4C modification of P16 mRNA to decrease its stability and expression intensity, and by altering the activity of the P16/CDK6/CCND1 axis in OGCs.

(E)-2-[2-(3-Fluoro-phen-yl)ethen-yl]quinolin-8-yl acetate.

In the crystal of the title compound, C(19)H(14)FNO(2), the mol-ecules are linked by C-H⋯O hydrogen bonds in translational chains along the b axis. The dihedral angles formed by the quinoline system with the fluoro-benzene ring and the acet-oxy group are 8.15 (3) and 77.42 (4)°, respectively.

[Predictability of the corneal flap creation with the femtosecond laser in LASIK].

OBJECTIVE: To observe the predictability of corneal flap creation with the FEMTO LDV femtosecond laser and analyze preliminarily the factors correlating to the thickness and diameter of the flap . METHODS: It was a study of serial cases. 260 eyes of 130 consecutive patients were treated with the FEMTO LDV. The eyes were assigned to two groups according to intended flap thickness, 110 µm (208 eyes) and 90 µm (52 eyes). Intended flap diameter varied from 8.5 to 9.5 mm. Difference analysis of flap diameter and intended diameter as well as flap thickness and intended thickness were made. The data was analyzed with SPSS to sum up a multiple stepwise regression formula that could express their quantitative relationship. RESULTS: The 90 µm flap group had a average flap thickness of (95.12 ± 7.65) µm, while for the 110 µm group the average flap thickness was (104.81 ± 3.09) µm. The difference between right and left eyes was not statistically significant (t(110 µm) = -1.223, t(90 µm) = -1.343, P > 0.05). Corneal flap thickness was inversely correlated with flap diameter (r(110 µm) = -0.143, r(90 µm) = -0.315, P < 0.05), but was not related to preoperative patient age, corneal thickness, keratometric value K or intraocular pressure (r(110 µm) = -0.160, 0.054, -0.011, -0.363; r(90 µm) = 0.024, 0.074, -0.212, -0.434, all P > 0.05). Corneal flap diameter was positively correlated with preoperative corneal keratometric value K and thickness (P < 0.001, P < 0.05). Multiple stepwise regression analysis showed flap diameter was an influencing factor for flap thickness. Preoperative corneal keratometric value K and thickness were influencing factors for flap diameter. CONCLUSIONS: The LASIK flap creation with the FEMTO LDV laser has relatively good predictability. Flap diameter is an influencing factor for flap thickness.

Anisomycin has a potential toxicity of promoting cuproptosis in human ovarian cancer stem cells by attenuating YY1/lipoic acid pathway activation.

Ovarian cancer is a highly malignant gynecologic tumor that seriously endangers women's health. We previously demonstrated that anisomycin significantly inhibited the activity of ovarian cancer stem cells (OCSCs) in vitro and in vivo. In the present study, anisomycin treatment of OCSCs significantly reduced ATP and T-GSH content; and increased pyruvate, LPO, and MDA. Anisomycin also significantly inhibited the proliferation of OCSCs in vitro, and its effect was similar to that of elesclomol and buthionine sulfoximine (BSO), suggesting that it has the potential to promote cuproptosis of OCSCs. Our subsequent cDNA microarray analysis results showed that anisomycin significantly reduced the transcriptional levels of genes that protect copper metabolism and cuproptosis, including the PDH complex, metallothionein, lipoid acid pathway, and FeS cluster proteins. Bioinformatics analysis revealed that four core factors (lipoic acid pathway FDX1, DLD, DLAT, PDH), and transcription factor YY1 were highly expressed in ovarian cancer tissues and were significantly correlated with an unfavorable prognosis. Further analysis depicted multiple YY1-recognized motif basic sites as existing in the promoters of the above four factors. In addition, the expression levels of YY1 in the tissue samples from ovarian cancer patients were significantly positively correlated with the expression levels of FDX1, DLD, DLAT, PDHB, and other genes. Finally, the analysis of the peripheral blood exosome database disclosed that the contents of the four key factors of YY1 and the lipoic acid pathway in the peripheral blood exosomes of patients with ovarian cancer were significantly elevated relative to those of normal healthy individuals. Therefore, our molecular biology experiments combined with bioinformatics analysis results suggest that the direct target of anisomycin-induced cuproptosis in ovarian cancer stem cells is probably a YY1 transcription factor. By inhibiting the expression and activity of YY1, anisomycin could not activate the transcriptional activity of the core genes of the lipoic acid pathway (i.e.,FDX1, DLD, DLAT, and PDHB), and induced the accumulation of cytotoxic substances, eventually leading to potential cuproptosis in ovarian cancer stem cells.

Yishen Xiezhuo formula ameliorates the development of cisplatin-induced acute kidney injury by attenuating renal tubular epithelial cell senescence.

Background: Although cisplatin (DDP) is an important clinical anti-tumor drug, its use is limited by its nephrotoxicity. How to avoid the renal injury incurred by platinum drugs and improve the clinical efficiency of platinum drugs use has become an urgent clinical problem. Previous studies have verified that Chinese medicine has definite effects on acute kidney injury (AKI). Yishen Xiezhuo formula (YSXZ) is a traditional Chinese medicine (TCM) compound which is an effective clinical drug for AKI, but its mechanism remains unclear. Methods: In our research, an AKI model was induced by DDP in human renal tubular epithelial cell (HKC) lines in the in vitro study. The mechanism of the YSXZ on cell senescence was analyzed by Cell Counting Kit-8 (CCK-8), senescence-associated ß-galactosidase (SA-ß-Gal) staining, western blot, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). Network pharmacology was used to analyze the role of YSXZ against AKI. Results: Compared with the control group, the cells in the DDP intervention group were significantly senescent. Compared with DDP group, YSXZ decreased the number of SA-ß-Gal-positive senescence cells, down regulated the expression of senescence-related proteins, reduced the release of senescence-related secreted phenotypic factors, and reversed the phenomenon of cell cycle S-phase arrest. Network pharmacology and experimental studies showed that the mitogen-activated protein kinase (MAPK) signaling pathway played a central role. Conclusions: Our present results suggested that YSXZ ameliorated the development of DDP-induced AKI by attenuating renal tubular epithelial cell (RTEC) senescence via alleviating the activation of MAPK pathway.

Chinese herbal medicine anticancer cocktail soup activates immune cells to kill colon cancer cells by regulating the gut microbiota-Th17 axis.

Chinese herbal medicines are effective for treating colon cancer (CC). CC development is reportedly associated with gut microbiota dysbiosis and immune function dysregulation. Herein we explored the therapeutic effects of a Chinese herbal medicine anticancer cocktail soup (CHMACS) on mice with CC and also explored its regulatory effects on gut microbiota. In vivo experiments indicated that CHMACS significantly inhibited the proliferation and tumorigenicity of CC cells. Further, CHMACS treatment decreased the proportion of CD8+ T, natural killer, and Th17 cells. HPLC/MS analysis showed that CHMACS comprised 227 active components. 16S rRNA sequencing revealed, for example, an increase in the relative abundance of uncultured_bacterium_g_Turicibacter and a decrease in that of uncultured_bacterium_g_Coriobacteriaceae_UCG-002 in gut microbiota of CHMACS-treated mice. Microbial diversity cluster analysis revealed that Verrucomicrobia, Spirochaetes, Fusobacteria, Patescibacteria, and Firmicutes contributed the most to fecal microbial diversity. Kyoto Encyclopedia of Genes and Genomes metabolic pathway analysis and clusters of orthologous groups of protein annotation indicated that CHMACS treatment induced amino acid metabolism and suppressed carbohydrate metabolism. Moreover, we found a strong association between changes in metabolites and immune cell maturation and activation. To summarize, our findings suggest that CHMACS kills CC cells by regulating gut microbiota and activating immune cells.